Long-Term Survival and Curative-Intent Treatment in Hepatitis B or C Virus-Associated Hepatocellular Carcinoma Patients Diagnosed during Screening.

Background: We initiated a prospective screening trial in patients with hepatitis to diagnose HCC in the early stage and to evaluate the impact on long-term survival. Methods: From 1993−2006, 10,372 patients with chronic hepatitis B (14%), hepatitis C (81%), or both (5%) were enrolled in an HCC screening program. All patients underwent liver biopsy at enrollment.

Early prediction of clinical response to checkpoint inhibitor therapy in human solid tumors through mathematical modeling.

Background: Checkpoint inhibitor therapy of cancer has led to markedly improved survival of a subset of patients in multiple solid malignant tumor types, yet the factors driving these clinical responses or lack thereof are not known. We have developed a mechanistic mathematical model for better understanding these factors and their relations in order to predict treatment outcome and optimize personal treatment strategies.

Methods: Here, we present a translational mathematical model dependent on three key parameters for describing efficacy of checkpoint inhibitors in human cancer: tumor growth rate (), tumor-immune infiltration (), and immunotherapy-mediated amplification of anti-tumor response ().

Use of human tissue stem cell-derived organoid cultures to model enterohepatic circulation.

The use of human tissue stem cell-derived organoids has advanced our knowledge of human physiological and pathophysiological processes that are unable to be studied using other model systems. Increased understanding of human epithelial tissues including intestine, stomach, liver, pancreas, lung, and brain have been achieved using organoids. However, it is not yet clear whether these cultures recapitulate in vivo organ-to-organ signaling or communication.

Perioperative Outcomes Following Combined Versus Isolated Colorectal and Liver Resections: .

Unlabelled: Our objective was to compare outcomes following combined versus isolated resections for metastatic colorectal cancer and/or liver metastases using a large, contemporary national database.

Background: Controversy persists regarding optimal timing of resections in patients with synchronous colorectal liver metastases.

Methods: We analyzed 11,814 patients with disseminated colorectal cancer and/or liver metastases who underwent isolated colon, rectal, or liver resections (CRs, RRs, or LRs) or combined colon/liver or rectal/liver resections (CCLRs or CRLRs) in the National Surgical Quality Improvement Program Participant Use File (2011-2015).

3D-Bioprinted Inflammation Modulating Polymer Scaffolds for Soft Tissue Repair.

Development of inflammation modulating polymer scaffolds for soft tissue repair with minimal postsurgical complications is a compelling clinical need. However, the current standard of care soft tissue repair meshes for hernia repair is highly inflammatory and initiates a dysregulated inflammatory process causing visceral adhesions and postsurgical complications. Herein, the development of an inflammation modulating biomaterial scaffold (bioscaffold) for soft tissue repair is presented.

Magnetic resonance imaging in the assessment of pancreatic cancer with quantitative parameter extraction by means of dynamic contrast-enhanced magnetic resonance imaging, diffusion kurtosis imaging and intravoxel incoherent motion diffusion-weighted imaging.

Background: Despite great technical advances in imaging, such as multidetector computed tomography and magnetic resonance imaging (MRI), diagnosing pancreatic solid lesions correctly remains challenging, due to overlapping imaging features with benign lesions. We wanted to evaluate functional MRI to differentiate pancreatic tumors, peritumoral inflammatory tissue, and normal pancreatic parenchyma by means of dynamic contrast-enhanced MRI (DCE-MRI)-, diffusion kurtosis imaging (DKI)-, and intravoxel incoherent motion model (IVIM) diffusion-weighted imaging (DWI)-derived parameters.

Methods: We retrospectively analyzed 24 patients, each with histopathological diagnosis of pancreatic tumor, and 24 patients without pancreatic lesions.

Glycofullerenes as non-receptor tyrosine kinase inhibitors- towards better nanotherapeutics for pancreatic cancer treatment.

The water-soluble glycofullerenes GF1 and GF2 were synthesized using two-step modified Bingel-Hirsch methodology. Interestingly, we identified buckyballs as a novel class of non-receptor Src kinases inhibitors. The evaluated compounds were found to inhibit Fyn A and BTK proteins with IC values in the low micromolar range, with the most active compound at 39 µM.

Single cell correlation analysis of liquid and solid biopsies in metastatic colorectal cancer.

As cancer care is transitioning to personalized therapies with necessary complementary or companion biomarkers there is significant interest in determining to what extent non-invasive liquid biopsies reflect the gold standard solid biopsy. We have established an approach for measuring patient-specific circulating and solid cell concordance by introducing tumor touch preparations to the High-Definition Single Cell Analysis workflow for high-resolution cytomorphometric characterization of metastatic colorectal cancer (mCRC). Subgroups of cells based on size, shape and protein expression were identified in both liquid and solid biopsies, which overall displayed high inter- and intra- patient pleomorphism at the single-cell level of analysis.

Sensing Temperature in Vitro and in Cells Using a BODIPY Molecular Probe.

Boron dipyrromethene (BODIPY) molecular rotors have shown sensitivity toward viscosity, polarity, and temperature. Here, we report a 1,3,5,7-tetramethyl-8-phenyl-BODIPY modified with a polyethylene glycol (PEG) chain, for temperature sensing and live cell imaging. This new PEG-BODIPY dye presents an increase in nonradiative decay as temperature increases, which directly influences its lifetime.

Radiofrequency Ablation and Microwave Ablation in Liver Tumors: An Update.

This article provides an overview of radiofrequency ablation (RFA) and microwave ablation (MWA) for treatment of primary liver tumors and hepatic metastasis. Only studies reporting RFA and MWA safety and efficacy on liver were retained. We found 40 clinical studies that satisfied the inclusion criteria.

Author Correction: A recellularized human colon model identifies cancer driver genes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Development of photoactive Sweet-C for pancreatic cancer stellate cell therapy.

Aim: Glycoconjugated C derivatives are of particular interest as potential cancer targeting agents due to an upregulated metabolic glucose demand, especially in the case of pancreatic adenocarcinoma and its dense stroma, which is known to be driven by a subset of pancreatic stellate cells.

Materials & Methods: Herein, we describe the synthesis and biological characterization of a hexakis-glucosamine C derivative (termed 'Sweet-C').

Results: Synthesized fullerene derivative predominantly accumulates in the nucleus of pancreatic stellate cells; is inherently nontoxic up to concentrations of 1 mg/ml; and is photoactive when illuminated with blue and green light, allowing its use as a photodynamic therapy agent.

National Failure of Surgical Staging for T1b Gallbladder Cancer.

Background: Current guidelines recommend radical cholecystectomy with regional lymphadenectomy (RC-RL) for patients with T1b gallbladder cancer (GBC). However, the extent to which these guidelines are followed is unclear. This study aimed to evaluate current surgical practices for T1b GBC and their implications for overall management strategies and associated outcomes.

Improved, Shorter-Latency Carcinogen-Induced Hepatocellular Carcinoma Model in Pigs.

Large animal models are important tools for hepatocellular carcinoma (HCC) research, especially in studies of hepatic vasculature, interventional techniques, and radiofrequency or microwave hyperthermia. Currently, diethylnitrosamine (DENA)-induced HCC in pigs is the only large animal model for in situ HCC with a tumor latency of 10-26 months. While phenobarbital (PB) is often used to accelerate DENA-induced HCC in rodents, it has not been previously studied in the porcine model.

Impact of the Treating Hospital on Care Outcomes for Hepatocellular Carcinoma.

Multidisciplinary hepatocellular carcinoma (HCC) treatment is associated with optimal outcomes. There are few data analyzing the impact of treating hospitals' therapeutic offerings on survival. We performed a retrospective cohort study of patients aged 18-70 years with HCC in the National Cancer Database (2004-2012).

Ultrasound Doppler as an Imaging Modality for Selection of Murine 4T1 Breast Tumors for Combination Radiofrequency Hyperthermia and Chemotherapy.

Noninvasive radiofrequency-induced (RF) hyperthermia has been shown to increase the perfusion of chemotherapeutics and nanomaterials through cancer tissue in ectopic and orthotopic murine tumor models. Additionally, mild hyperthermia (37°C-45°C) has previously shown a synergistic anticancer effect when used with standard-of-care chemotherapeutics such as gemcitabine and Abraxane. However, RF hyperthermia treatment schedules remain unoptimized, and the mechanisms of action of hyperthermia and how they change when treating various tumor phenotypes are poorly understood.

Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue.

Non-Invasive Radiofrequency Field Treatment of 4T1 Breast Tumors Induces T-cell Dependent Inflammatory Response.

Previous work using non-invasive radiofrequency field treatment (RFT) in cancer has demonstrated its therapeutic potential as it can increase intratumoral blood perfusion, localization of intravenously delivered drugs, and promote a hyperthermic intratumoral state. Despite the well-known immunologic benefits that febrile hyperthermia can induce, an investigation of how RFT could modulate the intra-tumoral immune microenvironment had not been studied. Thus, using an established 4T1 breast cancer model in immune competent mice, we demonstrate that RFT induces a transient, localized, and T-cell dependent intratumoral inflammatory response.

Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma.

[60]Fullerene is a highly versatile nanoparticle (NP) platform for drug delivery to sites of pathology owing to its small size and both ease and versatility of chemical functionalization, facilitating multisite drug conjugation, drug targeting, and modulation of its physicochemical properties. The prominent and well-characterized role of the enhanced permeation and retention (EPR) effect in facilitating NP delivery to tumors motivated us to explore vascular transport kinetics of a water-soluble [60]fullerene derivatives using intravital microscopy in an immune competent murine model of breast adenocarcinoma. Herein, we present a novel local and global image analysis of vascular transport kinetics at the level of individual tumor blood vessels on the micron scale and across whole images, respectively.

A new mild hyperthermia device to treat vascular involvement in cancer surgery.

Surgical margin status in cancer surgery represents an important oncologic parameter affecting overall prognosis. The risk of disease recurrence is minimized and survival often prolonged if margin-negative resection can be accomplished during cancer surgery. Unfortunately, negative margins are not always surgically achievable due to tumor invasion into adjacent tissues or involvement of critical vasculature.

The role of surgery and adjuvant therapy in lymph node-positive cancers of the gallbladder and intrahepatic bile ducts.

Background: Lymph node metastasis is a poor prognostic factor for biliary tract cancers (BTCs). The optimal management of patients who have BTC with positive regional lymph nodes, including the impact of surgery and adjuvant therapy (AT), is unclear.

Methods: This was a retrospective cohort study of patients who had T1-T3N1M0 gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHC) in the National Cancer Database (2004-2012).

Pancreatic adenocarcinoma response to chemotherapy enhanced with non-invasive radio frequency evaluated via an integrated experimental/computational approach.

Although chemotherapy combined with radiofrequency exposure has shown promise in cancer treatment by coupling drug cytotoxicity with thermal ablation or thermally-induced cytotoxicity, limited access of the drug to tumor loci in hypo-vascularized lesions has hampered clinical application. We recently showed that high-intensity short-wave capacitively coupled radiofrequency (RF) electric-fields may reach inaccessible targets in vivo. This non-invasive RF combined with gemcitabine (Gem) chemotherapy enhanced drug uptake and effect in pancreatic adenocarcinoma (PDAC), notorious for having poor response and limited therapeutic options, but without inducing thermal injury.